update: 16 Dec 2014 THE RISKS OF MODERN ANTIHYPERTENSIVE DRUGS: Pubmed search for ANTIHYPERTENSIVE DERMATITIS REACTIONS brings up >156 papers from 1970 (on practolol, propranolol, atenolol, labetolol, hydralazine, ACEI); we first encountered practolol (BBlocker) problems in the ’70s; and captopril (ACEI) dermatitis about 1980; Dermatitis has also been reported since 1987 with calcium channel blockers. WHY USE ACEI/ARBS and BETABLOCKERS -with their added airways and circulatory risks -EXCEPT AS LAST RESORT? when these are now routinely combined with other synthetic designer drugs clopidogrel (a sulfonamide) , or /and non-sulfonamide warfarin, aspirin, other NSAIDs and statins; sulphonylureas, glitazones, which cause serious multiple complications including dermatitis.

Refs: 1. Immunopharmacol Immunotoxicol. 2013 :35:447-50 “Cutaneous antihypertensiveadverse drug reactions (ADRs) have been frequently reported. Vena, De Simone ea University of Bari, Italy reported Eczematous reactions due to angiotensin-converting enzyme inhibitors ACEIs or angiotensin II receptor blockers ARBs in 23 hypertensive patients patients aged 66-87 years; 19 of them were taking another drug in addition to the suspected antihypertensive medication and 15 were on polytherapy with three or more drugs to treat multiple comorbidities. The antihypertensive culprit agents were (ACE) inhibitors in 9 patients, ACEI combined to hydrochlorothiazide (HCT) in 7 subjects, ARBs alone in 2 patients and associated with HCT in 5 cases. Eczema was generalized in 16 patients and localized in 7 cases, with predominant involvement of lower limbs. Such lesions developed after a latency of 4-30 months and were associated with moderate-to-severe itch, usually unresponsive to oral antihistamines. Histopathology was spongiotic dermatitis with possible associated psoriasiform skin changes.”

13 December 2014: latest analyses of all antihypertensive trials confirm that LOWDOSE (potassium-sparing) diuretic- eg amilozide- LOWDOSE reserpine, and if needed as 4th drug, calcium channel blocker eg amlodipine, each individually lower all major events including MORTALITY, ( and refractory lowers refractory pain). Betablockers, ACEI and ARBs do not reduce mortality- and have major adverse effects. .

Thomopoulos ea (Univs Athens & Milan) J Hypertens Dec 2014Effects of various classes of antihypertensive drugs on outcome incidence in hypertension,asks which BP-lowering drug classes are effective in reducing MORTALITY? In 55 RCTs (~200 000 individuals) all common antihypertensive drugs lowered BP , stroke, and major cardiovascular events; but in 2014 use, only a diuretic (even lowdose); and calcium antagonists gave significant reductions of all outcomes including mortality.

PAIN SUPPRESSED BY RESERPINE:S Afr Med J.1991;80:176-8. Significant cost-saving with modification of antihypertensive therapy. Keeton & Monteagudo, Univ.Cape Town. 30 patients on nifedipine for hypertension or chest pain were followed up for 6 months after alternative therapy- Reserpine combined with a thiazide- was instituted: blood pressure control improved and no serious side-effects were encountered. This reduced the monthly cost by 73%. Although a self-assessment depression inventory was completed by 21 patients, our study does not fully evaluate the impact on quality of life. The likelihood of side-effects is small–provided the maximum daily dose of reserpine does not exceed 0.1 mg. A more considered approach is needed in the choice of antihypertensive agents.

The progression of essential HBP begins with prehypertension in persons aged 10-30 years (by increased cardiac output) and then advances to early HBP in persons aged 20-40 years (increased peripheral resistance ), then to established HBP in persons aged 30-50 years, and finally to complicated HBP in persons aged 40-60 years.

Hence to prevent HBP becoming established and complicated by midlife, both the lifestyle/ nutritional factors, and the neural- stress and the RAAS renal-aldosterone- angiotensin systems – need to be optimized in young adulthood, in the early workplace if not childhood ie at school: with reintroduction at school of compulsory physical education/sport; banning of tobacco, refined sugar and retail salt sale; universal ingestion 3 times a week at least of a tsp of codliver oil equivalent (before it becomes unobtainable;) and a tblsp of virgin coconut oil; and if bloodpressure does not normalize, addition of at least 3 times a week 1/2 reserpine ie 0,125mg and 1/2 amilozide ie 27.5mg , to address most of the risk factors, as detailed below a week ago. .

Kostis ea, UnivHarvard; Rutgers,. Columbia,Texas, Am J Cardiol.2014 Feb examined Competing cardiovascular and noncardiovascular risks and longevity in the Systolic Hypertension in the Elderly Program SHEP with chlorthalidone-based stepped care (n = 2,365) or placebo (n = 2,371) for 4.5 years,. all participants were advised to take active therapy thereafter. At the 22–year follow-up, gain in life expectancy free from CV death in the active treatment group was 145 days ( p = 0.012). The gain in overall life expectancy was smaller (105 days)because of a 40-day (95% CI -87 to 161) decrease in survival from non-CV death. Compared with an age- and gender-matched cohort, participants had markedly higher overall life expectancy ( p = 0.00001) and greater chance of reaching the ages of 80 (81.3% vs 57.6%), 85 (58.1% vs 37.4%), 90 (30.5% vs 22.0%), 95 (11.9% vs 8.8%), and 100 years (3.7% vs 2.8%). In conclusion, Systolic Hypertension in the Elderly Program participants had higher overall life expectancy than actuarial controls and those randomized to active therapy had longer life expectancy free from CV death but had a small increase in the competing risk of non-CV death

The2013 Statement by the International & American Societies of Hypertension( including all continents and South Africa) includes amiloride-HCTZide ; and reserpine 0.1 mg/day in the array of drugs to be combined for optimal BP control. “Thiazide-like Diuretics: reduction of major cardiovascular CVD and stroke events have been established. Main side effects are metabolic (hypokalemia, hyperglycemia, hyperuricemia), which can be reduced by using low doses (eg, 12.5 mg or 25 mg of HCTZ) or by combining these diuretics with potassium-sparing agents eg angiotensin-blockers, amiloride etc . Note: Thiazides plus b-blockers are also an effective combination for reducing blood pressure, BUT since both increase blood glucose concentrations, use with caution in patients at risk for diabetes. Angiotensin-converting enzyme inhibitor ACEIs’ main side effect is cough (most common in women and in patients of Asian and African background). Angioedema is an uncommon but potentially serious complication that can threaten airway function, and it occurs most frequently in black patients.

Given the above -quoted longstanding established dangers of bblockers and ACEI; and that the majority of older State chronic patients around Cape Town are black and Asian women, overweight hypertensive diabetic smokers, it is negligence on the part of State authorities that most State patients are treated with deleterious betablockers (atenolol), Angiotensin blockers and HCTZ ; instead of primarily with the longproven optimal lowdose reserpine, amilozide and amlodipine.

30 Nov 2014 NEW studies below confirm that the renin-angiotensin-aldosterone system RAAS and the autonomic nervous systems ANS are the two networksthat primarily regulate bloodpressure. In baseline treatment of common essential HBP, Increasing recent research points to the prime role of amiloride – thiazide combination eg Moduretic, Amiloretic – and arginine (nitric oxide stimulant) – addressing the RAAS; – withreserpine addressing the ANS and anxiety.

and the cardiorespiratory risks of betablockers, and ARBs. The evidence in fact supports use of amiloride lowdose preventatively in a highrisk prehypertensive population. just as the prohormone metformin is used preventatively in reversing weight gain to prevent diabetes, atheroma and PCOS inferti9lity..

refs: 1. Nutr Hosp. 2014 Dec.ALDOSTERONE: A CARDIOMETABOLIC RISK HORMONE? Pereira , Bressan ea.University of Viçosa, Brazil.. Aldosterone is a component of the renin-angiotensin-aldosterone system, classically known for its role in sodium and water retention. Besides its renal effects, aldosterone is associated with the pathogenesis and progression of metabolic syndrome components. Diet can affect plasma aldosterone levels; high fructose and fat intake can lead to increased aldosterone levels, whereas the effect of sodium intake remains controversial. Adipose tissue, particularly visceral tissue, appears to produce a lipid-soluble factor that increases aldosterone production. Patients with metabolic syndrome have higher aldosterone levels; moreover, an increased cardiometabolic risk associated with insulin resistance could be partially mediated by the action of aldosterone via mineralocorticoid receptors. Even a subtle activation of this hormonal system may have deleterious effects on the glucose and lipid metabolism related to metabolic syndrome.

2. Semin Nephrol Sept 2014 .. Pathophysiology and Treatment of Resistant Hypertension: The Role of Aldosterone and Amiloride-Sensitive Sodium Channels.Judd EK1, Calhoun DA2, Warnock DG2. University of Alabama. Resistant hypertension is a clinically distinct subgroup of hypertension defined by the failure to achieve blood pressure control on optimal dosing of at least 3 antihypertensive medications of different classes, including a diuretic. In the absence of demonstrable renal, vascular and common endocrine causes, pathophysiology of hypertension can be attributed to aldosterone excess in more than 20% of patients with resistant hypertension. Dogma attributes increase in blood pressure seen with increases in aldosterone to its antinatriuretic effects. However, emerging research, has identified and defines the function of amiloride-sensitive sodium channels eNaC and mineralocorticoid receptors in the systemic vasculature, challenges impaired natriuresis as the sole cause of aldosterone-mediated resistant hypertension. It thus highlights the cardinal role of amilozide in hypertension therapy.

3. Pflugers Arch. 2014 Nov: Salt controls endothelial and vascular phenotype.Kusche-Vihrog , Brand ea. University of Muenster, Germany. High salt (NaCl) intake promotes development of vascular diseases independent of rise in blood pressure, whereas reduction of salt consumption has beneficial effects for the arterial system. We focus on endothelial Na+ channel (EnNaC)-controlled nanomechanical properties, since high Na+ leads to an EnNaC-induced Na+-influx and subsequent stiffening of endothelial cells. Mechanical stiffness of the endothelial cell (i.e., the endothelial phenotype) plays a crucial role as it controls the production of the endothelium-derived vasodilator nitric oxide (NO) which directly affects the tone of the vascular smooth muscle cells. In contrast to soft endothelial cells, stiff endothelial cells release reduced amounts of NO, the hallmark of endothelial dysfunction. This endothelium-born process is followed by the development of arterial stiffness (i.e., the vascular phenotype), predicting the development of vascular end-organ damage such as myocardial infarction, stroke, and renal impairment. In this context, we outline the potential clinical implication of arginine, direct (amiloride) and indirect (spironolactone) EnNaC inhibition on vascular function.

4. J Clin Hypertens (Greenwich). 2014 Jan Epithelial sodium channel eNaC inhibition by amiloride on blood pressure and cardiovascular disease risk in young prehypertensives.Bhagatwala , Dong ea, Regents University, Augusta, GA.. Overactivity of epithelial sodium channel (ENaC) is considered to be one mechanism underlying obesity-related blood pressure (BP) elevation. In a nonplacebo-controlled clinical trial , the authors aimed to comprehensively evaluate the effects of amiloride monotherapy, an ENaC blocker, on BP and cardiovascular risk in young adults with prehypertension (n=17). Following 10 mg daily amiloride for 4 weeks, peripheral systolic BP (SBP), central SBP, and carotid-radial pulse wave velocity were significantly reduced by -7.06±2.25 mm Hg, -7.68±2.56 mm Hg, and -0.72±0.33 m/s, respectively, whereas flow-mediated dilation was significantly increased by 2.2±0.9%. Following amiloride monotherapy for 4 weeks, a significant increase in serum aldosterone was observed (5.85±2.45 ng/dL). ENaC inhibition by amiloride may be used as an early intervention to halt the progression to full hypertension and cardiovascular disease in young adults with prehypertension.

6. Hypertension. 2012 .Double-blind, placebo-controlled, crossover trial comparing the effects of amiloride and hydrochlorothiazide on glucose tolerance in patients with essential hypertension. Stears, Brown ea University of Cambridge. Hypertension guidelines advise limiting dose of thiazide diuretics and avoiding combination with β-blockade, because of increased risk of diabetes mellitus. We tested whether changes in the 2-hour oral glucose tolerance test could be detected after 4 weeks of treatment with a thiazide and could be avoided by switching to amiloride. . For similar blood pressure reductions, there were opposite changes in glucose between the 2 diuretics (P<0.0001). There was a negative correlation between Δpotassium and Δ2-hour glucose (r=-0.28; P<0.0001). In 2 crossover studies, 4 weeks of treatment with a thiazide diuretic impaired glucose tolerance. No impairment was seen with K(+)-sparing diuretic or β(1)-selective blockade. Substitution or addition of amiloride may be the solution to preventing thiazide-induced diabetes mellitus.

7. Am J Physiol Endocrinol Metab. 2008 Dimethyl amiloride improves glucose homeostasis in mouse models of type 2 diabetes.Gunawardana , Piston ea .Vanderbilt University, Nashville, TN. Dimethyl amiloride (DMA) enhances insulin secretion in the pancreatic beta-cell. DMA also enhances time-dependent potentiation (TDP) and enables TDP to occur in situations where it is normally absent. As we have demonstrated before, these effects are mediated in part through inhibition of neuronal nitric oxide synthase (nNOS), resulting in increased availability of arginine. Thus both DMA and arginine have the potential to correct the secretory defect in diabetes by enabling or enhancing TDP. In the current study we demonstrated the ability of these agents to improve blood glucose homeostasis in three mouse models of type 2 diabetes. The pattern of TDP under different conditions indicates that inhibition of NOS is not the only mechanism through which DMA exerts its positive effects. Thus we also have explored another possible mechanism through which DMA enables/enhances TDP, via the activation of mitochondrial alpha-ketoglutarate dehydrogenase.

27 Nov 2014THE IMPORTANCE OF NORMALIZING RESISTANT HYPERTENSION : THE ALLHAT TRIAL Furberg ea December 2002 was the biggest trial that compared a thiazide with other standard antihypertensive drugs in highrisk patients, and confirmed thiazide’s superiority over amlodipine, lisinopril, and especially doxazosin. This was confirmed in the smaller shorter CONVINCE multinational trial Black ea a few months later, which showed that as single therapy, verapamil was inferior to a thiazide or atenolol.

24 Nov 2014NOTE how Big Pharma has lied in corrupting theWikipedia section (in italics below) onreserpine so as to try to further sideline this excellent natural drug: the adverse highlights below in red are based on ancient data from when Reserpine was used decades ago in the West in 5 to 50 times higher doses than have been used without adverse effects in trials the past 20 years, and for centuries in India as the parent Rauwolfia:

Reserpine: “because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely used today.Nonsense. This ignores the numerous side-effects of betablockers, ACEI, ARBs and CCBs other than amlodipine. The reserpine-induced depression is considered by some researchers to be a myth, while others claim that teas made out of the plant roots containing ie lowdose reserpine has a calming, sedative action that can actually be considered antidepressant.[4] Notably, reserpine was the first compound shown to be an effective antidepressant in a randomized placebo-controlled trial.[5] It may take the body days to weeks to replenish the depleted VMAT, so reserpine’s effects are long-lasting- a major advantage if patients take drugs irregularly. Tryptophan is the starting material in the biosynthetic pathway of reserpine, and is converted to tryptamine by tryptophan decarboxylase enzyme. Various enzymatic conversion reactions lead to the synthesis of reserpine from strictosidine.[8]

“This depletion of dopamine can lead with reserpine overdose to drug-induced parkinsonism. THIS IS ONLY IN EXCESSIVE RESERPINE DOSE. Reserpine has been discontinued in the UK for some years due to its numerous interactions and side effects. nonsense– it was discontinued to protect Big Pharma newer antihypertensive drugs eg Cardura, metoprolol, lisinopril; ARBs, Exforge etc .

“THE Reserpine-THIAZIDE COMBINATION (WITH OR WITHOUT OTHER OLD DRUGS EG POTASSIUM-SPARERS AND HYDRALAZINE) is one of the few antihypertensive medications that have been shown in randomized controlled trials to reduce mortality:

“Reserpine is rarely used in the management of hypertension today.NONSENSE – that is merely the explicit wish and intent of Big Pharma. Reserpine is listed as an option by the JNC 7.[17] Reserpine is a second-line adjunct agent for patients who are uncontrolled on a diuretic when cost is an issue.[18] The daily dose of reserpine in antihypertensive treatment is as low as 0.1 to 0.25 mg – IN FACT 0.0625 t0 0,125MG/d. At doses of less than 0.2 mg/day, reserpine has few side effects, the most common of which is nasal congestion- SO WE NEVER PERSIST WITH above 0.125mg/d

Nine years ago we reviewed in the BMJ why reserpine plus thiazide is The best-proven two-drug hypertension regime in primary care,

update 20 Nov 2014 the Sept 2014 influential French review Prescrire Intreviews the available evidenceTreating essential hypertension- As in 2004, the first choice is usually a thiazide diuretic TZD .. The current treatment threshold for hypertensive adults without diabetes or cardiovascular or renal disease is blood pressure above 160/90-100 mmHg. Apart from certain diuretic-based combinations, the use of combinations of antihypertensive drugs as first-line therapy has not been evaluated in terms of the complications of hypertension. systematic meta-analyses of tens of thousands of patients have compared the main classes of antihypertensive drugs against each other and against placebo. Compared with placebo, only low-dose TZDs and angiotensin-converting enzyme (ACEI) inhibitors have been shown to reduce all-cause mortality in hypertensive patients. They prevent about 2 to 3 deaths and 2 strokes per 100 patients treated for 4 to 5 years. Systematic reviews conclude that neither calcium-channel blockers CCBs, ACEI nor beta-blockers BBs are more effective than thiazide diuretics TZDs in reducing mortality or the incidence of stroke. The efficacy of the TZD chlorthalidone is supported by the highest-level evidence, three comparative clinical trials versus placebo, an ACEI, or a CCB, in more than 50 000 patients. In one of these trials, chlorthalidone was superior to the ACEI lisinoprilin preventing stroke; and to the CCB amlodipine in preventing heart failure. The effect of hydrochlorothiazide HCTZ , combined with amiloride or triamterene, on cardiovascular morbidity and mortality has been demonstrated in three comparative clinical trials versus placebo, BBs, or a CCB. HCTZ appeared more effective than the BB atenolol in reducing the incidence of coronary events. Indapamide another TZD is less convincing that it is more effective than chlortalidone or HCTZ. None of the antihypertensive drugs appears to have a better overall adverse effect profile than the others. Thiazide diuretics can provoke hyperglycaemia and diabetes, although this does not reduce their efficacy in the prevention of cardiovascular events. As in 2004, in 2014, the first-choice treatment for hypertension in nondiabetic adults without cardiovascular or renal disease should be a thiazide, possibly combined with amiloride or triamterene. When a diuretic cannot be used, it is better to choose an ACEI: captopril, lisinopril or ramipril.

But TZDiuretic halflife is at best 15hrs (HCTZ); and for smoother hypertension control they need to be gentle and not major diuresis-inducing, so that they do not disturb sleep or daytime function. and TZDs dont damp down compensatory heart speedup and arrhythmia, or lipidemia-hyperglycemia- which reserpine does. and lowdose reserpine doesnt cause the cough or breathlessness that ACEI, ARBs or BBs may.

This review needs to be read with Shamon & Perez‘ 2009 University of British Columbia Canadian Cochrane report : the first systematic review of reserpine for essential hypertension: “Many antihypertensive agents exist today for primary hypertension (systolic blood pressure >/=140 mmHg and/or diastolic blood pressure >/=90 mmHg). Reserpine was a second-line therapy in some of those trials. Included studies were truly randomised controlled trials comparing reserpine monotherapy to placebo or no treatment in patients with hypertension. MAIN RESULTS: Four RCTs (N =237) were found that met the inclusion criteria. The overall pooled effect demonstrates a statistically significant systolic blood pressure (SBP) reduction on reserpine compared to placebo (WMD –8mm, 95% CI -14.05, -1.78). None of the included trials reported withdrawals due to adverse effects. AUTHORS’ CONCLUSIONS: Reserpine is effective in reducing SBP roughly to the same degree as other first-line antihypertensive drugs. But this analysis is outdated because it has long been common cause that the best firstline treatment of hypertension is the balanced combination of reserpine with a potassium-sparing diuretic.

Hence combining lowdose eg 0.125mg/d or less reserpine – even 3 days a week ie 0.05mg/d- with amilozide 13-27mg/d as a morning or midday dose is ideal- especially when nighttime systolic hypertensionNSBP is the strongest predictor of CVEs cardiovascular events, as shown in a new international study in Europe, Brazil, and Japan by Universities of USA, UK and Europe: Roush, Zamalloa ea The ABC-H Investigators ; Journal of Hypertension (Oct 2014) Prognostic impact from clinic, daytime, and night-time systolic blood pressure NSBP in nine cohorts of 13 844 patients with hypertension;To determine which SBP measure best predicts cardiovascular events (CVEs- coronary artery disease CAD and stroke) independently, systematic review was conducted for all patients with hypertension,>1+ years follow-up.. Nine cohorts (n = 13 844) were from Europe, Brazil, and Japan. Results: Overall, NSBP’s dispersion exceeded DaySBP’s dispersion by 22.6% with nonoverlapping confidence limits. Within all nine cohorts, dispersion for NSBP exceeded that for ClinicSBP and DSBP ( P = 0.004) Considered individually, increases in NSBP, DSBP, and CSBP each predicted CVEs: hazard ratios (95% confidence intervals) = 1.25 (1.22-1.29), 1.20 (1.15-1.26), and 1.11 (1.06-1.16), respectively. However, after simultaneous adjustment for all three SBPs, hazard ratios were 1.26 (1.20-1.31), 1.01 (0.94-1.08), and 1.00 (0.95-1.05), respectively. Cohorts with baseline antihypertensive treatment and cohorts with patient-specific information for night-day BP classification gave similar results. Within most cohorts, simultaneously adjusted hazard ratios were greater for NSBP than for DSBP and CSBP: In hypertensive patients, NSBP had greater dispersion than DSBP and CSBP in all cohorts. On simultaneous adjustment, compared with DSBP and CSBP,increased NSBP independently predicted higher CVEs in most cohorts, and, overall, NSBP independently predicted CVEs, whereas CSBP and DSBP lost their predictive ability entirely. This trial confirms the 2012 Hosomi eaJapanese trial showing that to minimize (repeat) stroke from night BP variance, Antihypertensive medication taken in the evening or at bedtime is the most effective in treating morning hypertension when the patient adheres to the medication regimen.

There is no evidence in chronic treatment of common essential hypertension to justify loop diureticseg furosemide , as is common practice locally. .

update 12 Oct 2014For the past decade we have advocated for uncomplicated patients the gold-standard evidence-based combination of reserpine 0.0625 to 0.125 mg with 1/4 Amilozide (ie hydrochlorothiazide HCTZ 12,5mg and amiloride 1.25mg) ie HAR daily as the most cost-efficient baseline treatment of hypertension. Sometimes patients require the lower doses 1/4 tab each reserpine and Amiloretic 55mg) only 3 times a week for good control once on some cod liver oil, coconut oil and multivite-multimineral to reverse arteriosclerosis, insulin resistance, reactive oxygen species, and promote nitric oxide.

For more resistant cases we add dihydralazine 25 mg/d or amlodipine 5 to 10mg as add-ons if required – if necessary both- occasionally for optimal HBP control around 120 to 130 systolic (the new international Guideline target). With this regime of up to five drugs all more than 40 years in use, for hypertension we rarely find need to add the more costly / troublesome old eg methyldopa, or betablockers, spironolactone, or new eg ACEI or ARBs , with their cardio-respiratory risks that are so rare with the multi-low dose reserpine- amilozide- amlodipine- dihydralizane combination.

There are now 250 000 antihypertensive drug studies on Pubmed since 1947.

The latest and definitive study published on reserpine for HBP in Clin Drug Investig. 2011;31:769-77 is Long-term efficacy and tolerability of a fixed-dose combination of antihypertensive agents: an open-label surveillance study in China a massive 3 year (4500 patient-years) study by Wu Y, Li L. ea of Peking University Health Science Center, China . A fixed-dose combination (FDC) of four compounds, hydrochlorothiazide HCTZ 12.5 mg, triamterene 12.5 mg, dihydralazine 12.5 mg and reserpine 0.1 mg (HTDR), is widely used as an antihypertensive treatment in China. Although used in China for more than 30 years, there have been few comprehensive evaluations of this treatment. METHODS open-label surveillance study in Shanghai in local primary healthcare settings. Subjects with essential hypertension, aged ≥35 years at the time of enrolment. Patients with secondary hypertension, myocardial infarction or stroke within 6 months of screening, impaired renal or hepatic function, history of cardiomyopathy or chronic heart failure, or were pregnant or lactating were excluded. HTDR was administered as one or two tablets per day in the morning. If necessary, additional HCTZ was added. Blood pressure (BP) was measured every 3 months. RESULTS: A total of 1529 patients (65% female; mean age 65.7 years) entered the study with mean BP 149/89. After the 36-month treatment period, 93.1% of patients had achieved the SBP target, 97.9% had achieved the DBP target, and 92.1% had achieved both. The mean decreases in SBP and DBP were 15.3 mmHg and 9.9 mmHg, respectively. Overall, 127 adverse events in 119 patients (7.8%) occurred during the follow-up period, most of which were mild to moderate. Plasma lipids, uric acid and potassium improved. CONCLUSION: HTDR was found to have good long-term efficacy and tolerability in Chinese patients with essential hypertension.

The mean 15/10 BP lowering from a mean baseline BP of 149/89 after 3 years of the four-drug Chinese combination in China compares starkly with the mean ~51/30 mm Hg lowering (from untreated HBP of 200/120 down to ~149/90) over 4 months reported below by Alan Taylor in his 1989 thesis study in local rural Africans with similar doses of reserpine, HCTZ and dihydralazine- Taylor’s study achieving in rural Blacks in 4 months the starting BP of the Chinese some 25 years later. But the long Chinese study speaks to to the tolerance of the HTDR combination.

The China reserpine study of 1500 pts, 4500 pt years, strongly complements the ~13 trials of reserpine between 1977 (the Veterans’ Admin trial) and 1997(the German reserpine research group trials) in 7500 patients for 1 to 3 years; showing that low dose reserpine (and lowdose thiazide ) together are as good as or better than all more modern drugs- especially when augmented by amiloride.

(As Prof YK Seedat reported here in 2000), the China paper reports zero noteworthy dihydralazine risks at 12.5mg/d : J Hum Hypertens. 2000 ;14:739-47. Hypertension in developing nations in sub-Saharan Africa.Seedat YK. University of Natal, South Africa. There is a rapid development of ‘second wave epidemic’ of cardiovascular disease that is now flowing through developing countries and the former socialist republics. It is now evident from WHO data that coronary heart disease and cerebrovascular disease are increasing so rapidly that they will rank No. 1 and No. 5 respectively as causes of global burden by the year 2020. In spite of the current low prevalence of hypertensive subjects in some countries, the total number of hypertensive subjects in the developing world is high, and a cost-analysis of possible antihypertensive drug treatment indicates that developing countries cannot afford the same treatment as developed countries. Control of hypertension in the USA is only 20% (blood pressure <140/90 mm Hg). In Africa only 5-10% have a blood pressure control of hypertension of <140/90 mm Hg. There are varying responses to antihypertensive therapy in black hypertensive patients. Black patients respond well to thiazide diuretics, calcium channel blockers vasodilators like alpha-blockers, hydralazine, reserpine and poorly to beta-blockers, angiotensin-converting enzyme inhibitors and All receptor antagonists unless they are combined with a diuretic. There are social, economic, cultural factors which impair control of hypertension in developing countries. Hypertension control is ideally suited to the initial component on an integrated CVD control programme which has to be implemented. The existing health care infrastructure needs to be orientated to meet the emerging challenge of CVD, while empowering the community through health education.

Interestingly, a new metaanalysis of HCTZ trials by Musini ea Cochrane Database Syst Rev. 2014 May Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. shows that BP lowering over the dose range 6.25 mg, 12.5 mg, 25 mg and 50 mg/day is 4/2 mmHg, 6/3 mmHg, 8/3 mmHg and 11/5 mmHg, respectively. For other thiazide drugs, the lowest doses studied lowered blood pressure maximally and higher doses did not lower it more. Due to the greater effect on systolic than on diastolic blood pressure, thiazides lower pulse pressure by 4 mmHg to 6 mmHg. This exceeds the mean 3 mmHg pulse pressure reduction achieved by ACE inhibitors, ARBs and renin inhibitors, and the 2 mmHg pulse pressure reduction with non-selective beta-blockers as shown in other Cochrane reviews.

2009:ABSTRACT: When modern antihypertensive drugs cost far more than the old and tried, and have around 40% risk of adverse effects (Girerd 2002 Paris), and give inferior risk reduction, it is unethical for routine hypertension patients initially to be prescribed modern drugs singly or in combination in uncomplicated cases before trying the gold standard old risk-free lowdose reserpine-amilozide combination.

2009 has been a landmark year of published studies on first-line hypertension treatment.

iii. genetics and the above risk factors aside, three of the primary “endogenous” and easily correctable causes of essential hypertension are water deficiency; marine omega3 (EPA eicosapentanoic and DHA docosahexanoic acid) deficiency; and insulin resistance if not frank adiposity/overweight and diabetes.

So adequate water intake, and fish oil, and metformin/galega to tolerance, (in appropriate adipose/overweight cases) are cornerstones of antihypertensive therapy along with diet and lifestyle changes before any antihypertensive drugs are added.

Recently there have been contentious suggestion (eg Law and Ward UK 2009) that target bloodpressure should be that of youth- 120/70 down to 100/60 – as long as it does not fall so low that the patient gets dizzy on standing up. But the non-contentious gold standard remains that no one should be left with bloodpressure above at most 140/90 sitting.

ANTIHYPERTENSIVE DRUGS: There are over 34 000 RCTs, reviews and metaanalyses (since 1965) on Pubmed on these drugs.

Controlling hypertension asymptomatically before it causes damage and symptoms is the heart of successful prevention.

It is now claimed that hypertension risk starts as low as >120/70, that we should be targeting this level if tolerated.

This can only be done gently and slowly, if possible by optimising diet , lifestyle and natural supplements.

But prevention in asymptomatic patients must especially be at most a once-a-day regime, and avoid causing symptoms, and still give stable cover even if taken erratically. Only reserpine provides gentle cover lasting weeks, thus avoiding wide BP variation due to erratic dosing.

Apart from the notorious adverse effects of the older antihypertensives like guanethidine, methyldopa and atenolol, search of Pubmed under ‘ARBs, ACEI Cough;’ and under metaanalysis ‘antihypertensive cough’ with the established drugs, reveals 10 abstracts since the mid 1990s.

The nub of the matter is, the lowest-cost multiple-combination therapy (lowdose reserpine -amiloride – hydrochlorothiazide) gives the best bloodpressure and risk reduction with zero adverse effects – especially when combined with probably the best pluripotential drug of all, fish oil.. A new Cochrane metaanalysis from Univ Brit Columbia confirms that lowdose thiazide gives the best reduction of all antihypertensives in both all-morbidity and mortality outcomes -RR 0.89 (CI 0.82-0.97, p=0.0067 = highly significant) . And that metaanalysis didn’t deign to mention reserpine in the abstract.

There are at least a dozen trials each of reserpine and thiazide showing that they are the best, ideally in lowdose combination . As always, one fixed-dose combination pill (eg Brinerdin, Rautrax Imp) may work for many. But it is both cheaper, more efficient and scientific to prescribe the components separately so that reserpine and amilozide can each be titrated individually to tolerance, starting with eg reserpine (0.25mg tab ) 1/4/day and amilozide (55mg tab) 1/4 a day (costing locally retail perhaps US$0.5/month, $6/year) …

In some patients eventually this dose 3 days a week is all that is needed. With sensible advice about omitting sugar and smoking, and minimal alcohol, salt and cooked fats, and adding a multinutrient including magnesium, vitamins and the many favourable biologicals (including appropriate physiological sexhormone replacement), few patients need more than 1/2 a tab each of reserpine and amilozide for optimal BP and metabolic-vascular risk control. In the rare still- resistant cases, amlodipine is the next safest effective antihypertensive drug to add, starting with 2.5mg/d. But of course in those with insulin resistance (ie most cases), metformin is the most appropriate pluripotential drug.

Yet no trial has shown lower cost, and better superiority and safety of any modern-drug or combination over the triple-combination lowdose amilothiazide (thiazide since 1956, amiloride since 1967) with lowdose reserpine (from the ages-old rauwolfia – extracted as reserpine since 1949). Since the German Reserpine trials, and results of ALLHAT and SHEP showing that reserpine as add-on gave by far the best clinical outcomes, no head-on trials against modern drugs dare be done by drug companies or the clinicians they employ.

In 1989 pharmacist Alan Taylor published his MPharm thesis (Rhodes University) on Cost Effective Antihypertensive Therapy at A Day Hospital. – showing in a prospective randomized controlled trial for 4 months that stepped outpatient care (starting with a mean untreated BP of about 200/120) achieved the target BP ( then <165/95) in 73% compared to 11.5% on individualized treatment, and with a cost saving of 36%, with somewhat lower incidence of side effects. Hydrochlorothiazide HCT 12.5 to 25mg/d was the first step; methyldopa 250-500mg/d or reserpine 0.1mg/d as the 2nd; hydralazine 10-50mg/d low dose as the 3rd, alternatively atenolol 100mg as the 3rd or 4th step. Individualized treatment reduced bloodpressure by a mean 32.6/19 whereas stepped-care did so by 51.6/29.5mm Hg.. The HCT-Reserpine- Hydralazine-atenolol regime was the most frequently prescribed (in 61.6%),

Obviously today methyldopa, hydralazine and atenolol have become last-ditch add-ons, with amlodipine being the 1st- choice 4th drug to add to reserpine and amilozide. ,

and in 2007 Rayner, Blockman ea from the Hypertension Clinic at Groote Schuur Hospitalfound that at two community health clinics in Cape Town, only 40% of patients achieved a bloodpressure below 140/90, on a mean of 2.4 drugs per patient – clinics where reserpine and amilozide were unwisely removed from the available drug list years ago, for no plausible reason, leaving hydrochlorothiazide, atenolol, hydralazine and amlodipine as the choices- with invariably poor results in poor patients attending such free clinics.

MODERN DRUGS? But why should patients be subjected to the multiple and indisputable major risks of modern antihypertensive drugs compared to the gold standard lowdose reserpine and low dose amilozide?

From the trials and experience, lowdose amlodipine is certainly the modern drug of choice to add if counselling plus ceiling doses of reserpine and amilozide, plus fish oil plus metformin for underlying adiposity/insulin resistance, do not adequately control hypertension and other risk factors.

Why use modern drugs with their major potential hazards except for special circumstances last ditch?; when lowdose reserpine plus lowdose amilozide titrated to best effect rarely need a 4th drug added for good BP control; and practically – unlike methyldopa, guanethidine and more modern drugs- never causes persisting symptoms.

THIAZIDE ADVERSE EFFECT possible in even very low dose: anaphylaxis: Goetschalckx ea in 2007 could find exactly 49 case reports of allergic thiazide-induced pulmonary oedema in the literature after 50 years of use ie millions of patient-years. Thiazides are obviously sulphonamides, but fortunately serious- anaphylactic- reactions like lupus vascullitis and shock – are extremely rare. Wikipedia does not even mention these under thiazides, and no abstracts on Pubmed even guess at their rare incidence. 50 cases in at least 10million patient years is an incidence of below 5 per million.

We last year examined closely the trials on thiazides and reserpine 1, 2, 3.

and we published on line the only ever tabulation of all accessible trials of thiazides and reserpine, showing in the ~12 thiazide trials between 1985 (the UK MRC trial) and 2003 (the CONVINCE trial) that in 115000 patients for a mean of 4 years, thiazide is as good as or better than all more modern drugs;

and that reserpinein ~13 trials between 1977 (the Veterans’ Admin trial) and 1997(the German reserpine research group trials) in 7500 patients for 1 to 3 years is as good as or better than all more modern drugs. Of course the 2003 ALLHAT and CONVINCE papers were by far the biggest trials validating thiazide as the gold standard in 50 000 patients for 3 and 5 years respectively;

and the VA trials of 1977, 1982 and and 1990 in 1479 patients showing reserpine as equal or superior to betablockers, and the German trials of 1997 in 400 patients (Griebenow, Pittrow ea 1997) validating reserpine as equivalent to thiazide or a CCB, and the combination of thiazide and reserpine superior to an ACEI.

Now in 2009:

Shamon ea’s Cochrane review last month confirms that reserpine alone is at least equivalent in antihypertensive effect to any modern first line antihypertensive alone ;

Wald and Law’s metanalysis of single or combination antihypertensives confirms that “The extra blood pressure reduction from combining drugs from 2 different classes is approximately 5 times greater than doubling the dose of 1 drug.”

Hoffman ea’s review from New York confirms that, in autopsies of Alzheimer cases, those on antihypertensives had far less plaques that those without hypertension.

Sozen ea confirms that “ABs- Drugs with blocking effects on the renin-angiotensin-aldosterone system – do not improve endothelial dysfunction long-term in hypertensive patients”.

Mackenzie ea’sComparison of the effects of antihypertensive agents on central blood pressure and arterial stiffness in isolated systolic hypertension shows that central Pulse Pressure was only reduced significantly by perindopril, lercanidipine, and bendrofluazide, whereas atenolol had no effect. Lercanidipine reduced the augmentation index, whereas atenolol increased it. Aortic pulse wave velocity was not changed by any of the drugs. In summary, despite similar reductions in peripheral systolic and PPs with the 4 classes of drug, changes in central pressure and augmentation index varied. Because central PP and increased wave reflections are considered important risk factors in patients with isolated systolic hypertension, the choice of therapy may be influenced by these findings in the future.”

CONCLUSION: Reserpine has indisputable central and peripheral benefits in lowering central pressure via peripheral vasodilation, and via mild lowering of anxiety, cardiac rate and cardiac output; while thiazide and amiloride both lower both excessive body salt and water, while thiazide vasodilates and conserves calcium, and amiloride reverses the potassium -magnesium depletion seen in hypertension and with thiazide. .

Since the lowdose combination of reserpine and amilozide is superior to all other first-line drugs alone or in combination, and retail costs about US$1 a month in South Africa, (with negligible adverse effects compared to all other antihypertensive drugs), this combination is the mandatory firstline therapy for all hypertensive patients, with rare exceptions. This regime starts with amilozide 13.75mg (1/4 tab) and reserpine 0.0625mg (1/4tab) /d- and many patients can eventually be controlled with these doses just 3 days a week; with other antihypertensives added only if hypertension is not controlled with these increased to the ceiling tolerated eg of amilozide 27.5mg/d and reserpine 0.125 mg/d (maximum reserpine 0.25 mg 5/week ie 0.18mg/d if tolerated).

Since roleplayers are there to serve patients, not the Drug and Disease Industry, all roleplayers ( National Hypertension societies, provincial and national health and medical school authorities, medical schemes and all health practitioners) have no choice but to obey the gold-evidence-based medicine set out herein, and reinstate reserpine and amilozide as mandatory 1st-line therapy of essential hypertension, with motivation for alternatives to be provided in the exceptional cases.

Unlike the USA and the East where reserpine is still in national recommendations, Authorities, regulators, suppliers and prescribers in South Africa, Australia, the UK and Europe can no longer continue to defraud the public and deny patients this best treatment, since the two tablets (cheap amilozide and reserpine) are freely and universally available for at most the retail South African prices quoted (less in bulk buy).

There is no shortage of reserpine, HCT or amiloride; and the evidence for them over all modern antihypertensives is binding under rules of evidence and therefore medical ethics. The current evidence discussed shows that this old lowdose combination is superior to all modern drugs and modern marketted combinations in both reduction of all-cause endpoints, adverse effects, and cost.

As Henry Black said recently, triple antihypertensive therapy is simply Back to the Past – and it can be both very low cost and risk-free..

And if proof is wanted, we must agree on a simple long term multicentre trial of the lowdose reserpine-amiloretic regime versus modern marketed combinations.- as in ALLHAT but comparing combinations..But who is to pay for yet another trial to prove what is already so well proven?

35 years after Illich’s Medical Nemesis, it is very sad to have to be fighting overwhelming profiteering vested interests for what is now by far the commonest and most easily correctable major common degenerative disease – mild to moderate hypertension.

Update: 6 May 2010: this week’s recall of Johnson and Johnson’s Tylenol, Motrin, Zyrtec, and Benadryl due to negligent contamination , in particular of Tylenol for children, leapfrogs America’s household favourite Johnson and Johnson J&J to 2nd place (with at least 6 bad drugs) in the fraudsters mafia roll of dishonour behind the unreachable leaders Pfizer with about a dozen notorious fraud drugs. What is another $81million fine to J&J that had sales of >$63billion in each of the last two years with profit of above 20%, and that despite the recall still maintained this turnover in quarterly sales for the 1st quarted this year?

The major thing is that despite J & J’s gross negligence endangering the lives of children, the FDA has taken no other action against them. They terrorize with armed marshalls for trivia and shut down small firms making safe health supplements and physicians using them, but the Big Pharma mafia are the darlings of the FDA and Government since they pay such vast amounts in fees and taxes to Govt and lobbyists- politicians and academicians- trialists – that they are untouchable in every country..

And now Harvard University shows that even Neurontin and lamotrigine increase the risk of suicide by42% and 81% respectively. So the long list of fraudulently overmarketed or hazardous -improperly registered or prescribed drugs without adequate trials or obligatory definite indications- grows.

Pfizer, Bayer, GSK and Roche with the 100% support of their respective government regulators and politicians continue to vie for top place as the biggest fraudsters of all time – competing with the food, tobacco, booze, media, vehicle, financial, lawyer, minerals, fuel and politics industries..

Why is this? Because the public – taxpayers and the poorer consumers- are at their most vulnerable, pawns if not cannonfodder and guineapigs when it comes to trust in government regulators and the giant consumer product industries – manufacturers and big distributors- that Govts regulate – especially the disease and drug industries.

And government regulators are controlled by elected politicians who ( apart from a few altruistic successful honest folk who stand out and are nominated for or called to office -but not Ralph Nader) – as mostly lawyers or failed businessmen/ workers or carreer trade unionists, rarely seek higher office except to further their own financial interests and power lust.

Winston Churchill and Frank Rooseveldt vie with Margaret Sanger, Mahatma Ghandi and Nelson Mandela for honour as the leading persistent (western) fighter for justice, human rights of the 20th century if not all time, since they were skillful – brave but above all tough enough (unlike many heroic martyrs) to survive to see it through.

Hence there is enormous incentive for collusion between politician/ government officials who control the taxes and spending thereof, and the big businesses that control the big money that escapes the tax officials – including Big Pharma. In South Africa there is no incentive whatsoever for the MCC Medicines Control Council Regulator to work efficiently as all income it generates is absorbed by the Fiscus/Dept Health, which blatantly refuse to produces annual financials for the MCC – effectively a parastatal supposedly under an independent CEO and Board.

Below is a list of costly modern disaster or dubious largely chronic drugs and their manufacturers that earn the profound distrust of consumers: (where there are a proliferation of me-too analogues in a group eg benzos, statins, NSAIDS, bisphosphonates, only the original one or two are listed since they led/lead the pack):

PFIZER -Wyeth -Searle – Upjohn:Neurontin; Geodon, Bextra, Zyvox, Lyrica; Lipitor; Celebrex; PremPro; aspartame; Rezulin; Viagra; and Ativan=lorazepam/ Xanor=alprazolam – two of the most addictive chronic “anxiolytic” benzos – again, in Wiki and MIMS their indications are far fewer than the pages of problems they cause us since the 1970s , papering over and masking symptoms by numbing the mind (as with alcohol and smoking) instead of patients addressing the underlying cause of their anxieties with psychotherapy including learning self-hypnosis control.

Collectively, Pfizer (the conglomerate of rash clones it has swallowed) has as many modern disaster/fraud drugs as the next two combined of its major league fraud competitors:

Eli Lilly – Prozac, Zyprexa; memantine ; and DES-diethylstilbestrol, perhaps the most infamous of all commercialized drugs in causing problems even in grandchildren of those so recklessly exposed to it without evidence of benefit. (Eli Lilly was the last company to stop manufacturing it – in 1997! despite evidence of it’s disasterous effects published in 1953, and of cancer from 1971 . )

Bristol-Myers Squibb -Pravastatin; Plavix, warfarin; And the sustained cover-up of the COSMIC metformin obligatory postmarketing trial done at the insistence of the FDA on a huge 9000 subjects for 1 year in about 1996/7. This trial was eventually submitted for publication only in 2004 and thus published in 2005- but for the previous year BMS and their licensor the original patent-holder Merck denied any knowledge of such a trial although the summary was presented and published a year earlier at a US diabetes congress by the authors, and we supplied the COSMIC abstract- written by BMS researchers who did the COSMIC trial- to BMS and Merck… . why would BMS and Merck delay publication of this trial for so many years, and blatantly deny knowledge of it after the first report of the trial result at a USA diabetes congress ?

The answer can only be the predicted- because it confirmed in the biggest metformn trial cohort ever- 8000 patient-years- that metformin in diabetics gave zero significant adverse drug effects, with the all-cause deathrate in fact 9% lower than in those on other conventional antidiabetic therapies; and four major diabetes prevention trials of metformin in four continents confirmed that it at least halves the incidence of new diabetes- with zero significant adverse effects; and in the intervening years between this trial and it’s result publication, both BMS and Merck developed and launched their respective combinations of metformin and a sulphonylurea (M + SU) . This despite the fact that it was clear since at least the 1970s that the addition of sulphonylurea to metformin is a desperate last resort since it is fraught with risk of hypoglycemia and reversal of the reduction in fatness produced by metformin alone.

A new retrospective study just published from the UK patient database confirms the folly known all along of combination of SU with metformin in that that over a mean of 4 years on therapy, the metformin+SU therapy reduced all-cause mortality by 23% compared to SU alone; while metformin alone compared to SU alone reduced mortality 1/3 more ie by 30% – with trivial risk of hypoglycemia. This was similar to the outcome in the 20year UKPDS RCT, where metformin reduced all-cause mortality by 36% over a mean of 13 years, making it the safest and most effective drug ever patented for chronic degenerative disease. .

And note the cynical folly of the many manufacturers of the grossly overpromoted and overprescribed bisphosphonates and statins – which have numerous serious adverse effects and should be last-ditch therapy in metastatic bone cancer and in rare serious hyperlipidemia, not for osteoporosis, not for mild to moderate lipidemia and certainly not over-the-counter as profiteers crave.

ENDURINGLY BENEFICIAL MODERN CHRONIC DRUGS:

The above drugs contrast with vey few modern chronic designer drugs that are still the leaders in their fields, whether as original or generic – although none of them has been shown to address all-cause mortality and pathogenesis.

Pfizer’s Norvasc=amlodipine is a rare modern designer exception – dating from the late 1980s, it’s patent has only just run out- proving it’s enduring worth for longterm hypertension therapy as the premier 4th-line drug to add when reserpine 0.125mg plus amiloretic 1/2 (ie HCT 25mg + amiloride 2.5mg) daily are inadequate for optimal control; with very low risk of serious adverse effects.

BMS’ Captopril & Merck‘s Renitec – angiotensin converting enzyme inhibitors ACEI – date from the mid-late ’70s, and while they were and are the first of the invaluable ACEI inhibitors, 5th line antihypertensive drugs for common use, they have formidable potential for lifethreatening adverse effects- but they are on essential drug lists. In the past dozen years big pharma has attempted to substitute angiotensin 11 receptor blockers ARBs, for the aging ACEI, but a recent metanalysis shows that neither group of drugs significantly lowers fatal or nonfatal cardiovascular events- and they all (unlike reserpine + coamiloretic + amlodipine) have risk of life-threatening adverse effects.

DRUGS FROM THE GOLDEN AGE:

Virtually all other current designer drugs of enduring and safe worth for chronic longterm use originated from the golden era of innovative and enduring designer drugs mostly around WW2 up to the 1960s:

The modern birth control OC pill taken chronically by millions of women for up to decades for either contraception or symptom control, certainly dates enduringly and endearingly from the post war Golden Era as Estinyl (Schering 1930s) , with or alternatively just a progestin. Modern preparations are relatively so safe that they are the preferred contaceptives for millions of young women. But we have just seen two young women unwisely started on Bayer-Schering’s Yaz/Yasmin develop in one case hypertension and major weight gain, the other hives- so such innovations are not necessarily better than established brands of OC .

Merck’s 80yr old metformin- the only laboratory – originated drug (a teak of the galega plant’s biguanide) that reduces all-cause mortality – by no less than 36%, without a single serious adverse effect or mortality if sensibly used;

Bayer’s Adalat; Aspirin (1899) ; prednisone;

Novartis-Ciba-Geigy– Imipramine-Tofranil the first successful commercialise and still enduring major antidepressant.

Pfizer -GDSearle’s Aldactone; Sulfasalazine; and the 100year old phenytoin -Dilantin, still a longterm lifesaving antiepileptic despite occasional major adverse effects.

Boot’s Brufen- the NSAID nonsteroidal anti-inflammatory drug on Essential Drug Lists, altho there is no evidence that this group of drugs is essenntial since they do not alter the course of the underlying chronic inflammatory disease or reduce longterm mortality and morbidity, are little if at all better than Panado+- codeine as painkillers, and have formidable risks. http://en.wikipedia.org/wiki/Ibuprofen#History

Astra-Zenca-ICIs Inderal was the first of the major new cardiovascular protectant beta-blockers which are essential drugs., altho all have formidable potential adversity ; as with ACEI, no special optimal favourite has yet emerged; they have some special chronic indicatiions, including heart conditions and special cases of hypertension. .

It is surely no co-incidence that virtually all the above common fraud-drug pharmacy companies are among the dozen top money-spinners listed on 2009 financials.. But perhaps the biggest racketeering of modern times has yet to be quantified, perhaps $100 billion of wasted money on last year’s swine flu “pandemic” that never happened, in futile mass screening lab tests and vaccines and Tamiflu – giving massive profits (some companies claimed >$6billion) with total indemnity against litigation to Roche, GSK, Novartis, Baxter, Sanofi et al.. The USA-dominated WHO hastily changed the core definition of pandemic early in the North American outbreak so it could declare the nonsensical pandemic to suit the pockets of the profiteering American-European conglomerate and the political lobbyists they employ in Government and beaurocracy…

So do we wonder why we can’t trust Big Pharma prescription drugs and doctors’ judgment? Read the stats of a 5years study of the relevant risks, of deaths from prescription drugs in USA ( versus natural supplements) exceeding over 106 000 to 1. Thats why Big Pharma and it’s “regulators” like the US Govt FDA, the UK MCC, European medicines Authority EMA, and organized doctors, are so desperate to stop the public buying the supplements people choose- when early and permanent use of balanced natural supplements at least halve serious disease and thus medical consultations, prescription drug use and hospitalization. For profit, only disease (not prevention) pays.

Of the 103 drugs that achieved $billion sales in 2006,: considering the chronic disease drugs, only valproate and J & J’s contraceptive dates back to the 1980s; Wyeth’s Premarin-Prempro dates back to 1995; and (omiting duplicate entries) only 33 were oral drugs for chronic major common degenerative (as opposed to infective or malignant or autoimmune ) diseases. And of the ~33 , only 10 (in descending order of sales value on that list) even vaguesly justified their ranking and sales- amlodipine, venlafaxine, bupropion, metoprolol, Viagra ,carvedilol, valproate, ramipril, paroxitine and premarin-

Reuter’s forecast of the 10 >$5billion raincheques for 2010 include in descending rank for common chronic diseases only the tablets Lipitor, Plavix, Diovan and Crestor- none of which are proven essential drugs for common average disease use. They are there solely because of heavy marketing by Big Pharma, despite their mediocre results and major potential risks, with far better results given by long-proven natural supplements or by lowdose reserpine-amiloretic combination, then amlodipine .

Finally, landmark drugs that were not invented by, or were laregly ignored by, suppressed by drug companies as medicinals:

Yet despite the vast evidence favouring fish oil, metformin and EDTA as perfectly safe and effective chronic anticoagulation, the Disease Industry persists in promoting rat poison- warfarin, dicoumarol– as the common chronic anticoagulant, despite its’ proven risks of promoting hemorrhage, fractures – already known since at least 1998 , vascular calcinosis already known since 1998 and most recently published last month; and even cancer .

Metforminis unique, the widest multidisease panacea ever extracted (from a traditional antidiabetic plant) and patented. Like EDTA it was eventually identified in 1922 by university researchers Werner and Bell in Ireland – but only patented and produced for routine diabetic use since the 1950s- and deliberately obstructed for use in the USA for another 40 years by the FDA and Big Pharma, which were busy as bees designing and mass marketing far less safe and effective USA sulphonylureas although these were already discredited by the UGDP almost 50 years ago, when metformin was ‘rediscovered’ and came into its own.

Reserpine also a plant (rauwolfia) extract remains (with coamiloretic, amilozide) both in low dose the first-line drug treatment of all classes of hypertension– which since the prevalence of this disease now approachines 50 % in aging adults, makes these drugs amongst the most prevalent essential drugs needed. As even wiki says, from many major studies over decades, “Reserpine is one of the few antihypertensive medications that have been shown in randomized controlled trials to reduce mortality” – in at least a score conclusive trials of the individual components reserpine, thiazide and amiloride, the triple combination is by far the best firstline therapy, at a cost in South africa of about $US1 a month.. . But Big Pharma and its profiteer lobbyists continue to suppress the combination fraudulently based on decades-old overdosage data.

By contrast well over 100 natural micronutrient substances – cinnamon, garlic, ginger, codeine, reserpine, digoxin, huperzine A, galega-metformin and many other plant extracts; vitamins especially B,C,D in higher dose; , minerals especially calmag, zinc, chromium, boron, iodine, iron and even lithium; and human biologicals that deplete with aging like glucochondroitin, CoQ10, acetylcysteine, arginine, cartnitine , GABA, 5HTP and almost 20 other hormones replaced chronically – provide almost every chronic major degenerative disease with the best prevention and treatment, without the almost invariable risks of the modern designer chronic drugs discussed above.

Since alcohol and tobacco, salt and sugar are still freely sold over the counter OTC without any restrictions except some to children , the commonest causes of chronic degenerative disease in more than slightest daily usage, it is obviously lowdose vitamin K, vitamin C and D, lithium, magnesium, reserpine, metformin- galega and EDTA that should be mandatorily supplemented in the food chain for the fattening aging 1st-world populations, and allowed OTC purchase; while indications are severely limited for prescription of sulphonylureas, statins, bisphosphonates and the dozens of other disaster or dubious designer drugs listed above.

The Medline review BetaBlockers in Hypertension today again raises this hoary question:

Why does one still continue to see patients on unnecessary atenolol and angiotensin converting enzyme inhibitors ACEIs for mild-to-moderate hypertension?

eg from public Day Hospitals, postmenopausal fat domestic maidservants with severe acute bronchitic cough; on atenolol 50mg/d, HCT hydochlorothiazide 25mg/d, enalapril 20mg ; & if needed hydralazine 50mg/d. They have usually never had any problem but obesity and thus related insulin resistance – hypertension- mild lipidemia, and painful knees. Thus what they need above all else is encouragement about weight loss- swopping sugar to eg stevia; cooked fats to a supplement of cod liver oil; and early supplement with permanent metformin to tolerance if they do not soon start to lose 1/2 kg weight a month.

It is surely criminal negligence that patients (especially the poor fat, prone to infections, acute asthma bronchitis and diabetes) are still being dispensed atenolol with 25mg/day HCT as first line therapy for hypertension, and enalapril and hydrazine as 2nd/third line; when

* atenolol (ie betablockade) has been confirmed not to have global benefit, and is therefore restricted strictly to specific types of heart disease; avoiding problems with eg diabetes; asthma; fatigue; impotence and depression;

Conversely, it has been known for many years- and repeatedly reviewed in this column- , seen every day in the poor and rich, that

* reserpine is the safest and best protectant of all hypertensive problems at a dose of 1/8 to 1/2 tablet ie 0.03 to 0.125mg day – mean about 0.625mg/d, with trivial if any adverse effects combined with

* co-amiloretic 1/8 to 1/2 ie 7 ie 7 to 25mg a day – mean about 13.5mg/d – potassium-sparing combination diuretic being the only antihypertensive which in the CACHE County study halved the incidence of dementia. (the standard available tablet is still 50mg HCT plus 5mg amiloride).

*amlodipine is the best if needed add-on “next-line drug “, with negligible adverse effects, if lowdose reserpine + amiloretic do not suffice. (It remains to be seen if carvedilol does any better than amlodipine long term – no comparative long term studies yet appear on Pubmed).

the doses of these are easily titrated downwards from if necessary the top dose as the bloodpressure settles gradually and safely. In the longterm low doses , they have no adverse effects.

At least two old (Finnish) studies (1, 2) show the risks of even 25mg HCT a day and with or without amiloride.

Do complaints of malpractice have to be lodged to have such adverse prescribing – dictated by senior academic doctors (whose research and travel is often funded by drug companies) – stopped, and all clinics supplied with what has been gold standard for hypertension for ages- reserpine and amiloretic tablets with an average retail monthly cost of R5 for good blood pressure control?